ID   NSCA_ARTGP              Reviewed;        1797 AA.
AC   E4V2N2;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   08-FEB-2011, sequence version 1.
DT   03-AUG-2022, entry version 55.
DE   RecName: Full=Non-reducing polyketide synthase nscA {ECO:0000303|PubMed:23758576};
DE            EC=2.3.1.- {ECO:0000305|PubMed:23758576};
DE   AltName: Full=Conidial yellow pigment biosynthesis polyketide synthase nscA {ECO:0000303|PubMed:23758576};
DE   AltName: Full=Neosartoricin B biosynthesis protein A {ECO:0000303|PubMed:23758576};
GN   Name=nscA {ECO:0000303|PubMed:23758576}; ORFNames=MGYG_06588;
OS   Arthroderma gypseum (strain ATCC MYA-4604 / CBS 118893) (Microsporum
OS   gypseum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Onygenales; Arthrodermataceae; Nannizzia.
OX   NCBI_TaxID=535722;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4604 / CBS 118893;
RX   PubMed=22951933; DOI=10.1128/mbio.00259-12;
RA   Martinez D.A., Oliver B.G., Graeser Y., Goldberg J.M., Li W.,
RA   Martinez-Rossi N.M., Monod M., Shelest E., Barton R.C., Birch E.,
RA   Brakhage A.A., Chen Z., Gurr S.J., Heiman D., Heitman J., Kosti I.,
RA   Rossi A., Saif S., Samalova M., Saunders C.W., Shea T., Summerbell R.C.,
RA   Xu J., Young S., Zeng Q., Birren B.W., Cuomo C.A., White T.C.;
RT   "Comparative genome analysis of Trichophyton rubrum and related
RT   dermatophytes reveals candidate genes involved in infection.";
RL   MBio 3:E259-E259(2012).
RN   [2]
RP   FUNCTION.
RX   PubMed=23758576; DOI=10.1021/sb400048b;
RA   Yin W.B., Chooi Y.H., Smith A.R., Cacho R.A., Hu Y., White T.C., Tang Y.;
RT   "Discovery of cryptic polyketide metabolites from dermatophytes using
RT   heterologous expression in Aspergillus nidulans.";
RL   ACS Synth. Biol. 2:629-634(2013).
CC   -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC       that mediates the biosynthesis of neosartoricin B, a prenylated
CC       anthracenone that probably exhibits T-cell antiproliferative activity,
CC       suggestive of a physiological role as an immunosuppressive agent
CC       (PubMed:23758576). The non-reducing polyketide synthase nscA probably
CC       synthesizes and cyclizes the decaketide backbone (By similarity). The
CC       hydrolase nscB then mediates the product release through hydrolysis
CC       followed by spontaneous decarboxylation (By similarity). The
CC       prenyltransferase nscD catalyzes the addition of the dimethylallyl
CC       group to the aromatic C5 (By similarity). The FAD-dependent
CC       monooxygenase nscC is then responsible for the stereospecific
CC       hydroxylation at C2 (By similarity). Neosartoricin B can be converted
CC       into two additional compounds neosartoricins C and D (By similarity).
CC       Neosartoricin C is a spirocyclic compound that is cyclized through the
CC       attack of C3 hydroxyl on C14, followed by dehydration (By similarity).
CC       On the other hand, neosartoricin D is a further cyclized compound in
CC       which attack of C2 on C14 in neosartoricin C results in the formation
CC       of the acetal-containing dioxabicyclo-octanone ring (By similarity).
CC       Both of these compounds are novel and possibly represent related
CC       metabolites of the gene cluster (By similarity).
CC       {ECO:0000250|UniProtKB:A1D8I9, ECO:0000250|UniProtKB:F2S6Z9,
CC       ECO:0000305|PubMed:23758576}.
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000250|UniProtKB:A0A0K0MCJ4};
CC       Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:23758576}.
CC   -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC       (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC       repeated decarboxylative condensation to elongate the polyketide
CC       backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC       transfers the extender unit malonyl-CoA; a product template (PT) domain
CC       that controls the immediate cyclization regioselectivity of the
CC       reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC       serves as the tether of the growing and completed polyketide via its
CC       phosphopantetheinyl arm (By similarity).
CC       {ECO:0000250|UniProtKB:Q5B0D0}.
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DR   EMBL; DS989827; EFR03594.1; -; Genomic_DNA.
DR   RefSeq; XP_003170602.1; XM_003170554.1.
DR   AlphaFoldDB; E4V2N2; -.
DR   SMR; E4V2N2; -.
DR   STRING; 63402.XP_003170602.1; -.
DR   EnsemblFungi; EFR03594; EFR03594; MGYG_06588.
DR   GeneID; 10025841; -.
DR   eggNOG; KOG1202; Eukaryota.
DR   HOGENOM; CLU_000022_6_1_1; -.
DR   InParanoid; E4V2N2; -.
DR   OMA; LNTHYDP; -.
DR   OrthoDB; 68112at2759; -.
DR   Proteomes; UP000002669; Unassembled WGS sequence.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.10.129.110; -; 1.
DR   Gene3D; 3.40.366.10; -; 2.
DR   Gene3D; 3.40.47.10; -; 1.
DR   InterPro; IPR001227; Ac_transferase_dom_sf.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR014043; Acyl_transferase.
DR   InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR   InterPro; IPR018201; Ketoacyl_synth_AS.
DR   InterPro; IPR014031; Ketoacyl_synth_C.
DR   InterPro; IPR014030; Ketoacyl_synth_N.
DR   InterPro; IPR032821; PKS_assoc.
DR   InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR   InterPro; IPR020807; PKS_dehydratase.
DR   InterPro; IPR042104; PKS_dehydratase_sf.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR030918; PT_fungal_PKS.
DR   InterPro; IPR032088; SAT.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF00698; Acyl_transf_1; 1.
DR   Pfam; PF16197; KAsynt_C_assoc; 1.
DR   Pfam; PF00109; ketoacyl-synt; 1.
DR   Pfam; PF02801; Ketoacyl-synt_C; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   Pfam; PF14765; PS-DH; 1.
DR   Pfam; PF16073; SAT; 1.
DR   SMART; SM00827; PKS_AT; 1.
DR   SMART; SM00825; PKS_KS; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   SUPFAM; SSF52151; SSF52151; 1.
DR   SUPFAM; SSF53901; SSF53901; 1.
DR   TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR   PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   3: Inferred from homology;
KW   Acyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW   Phosphoprotein; Reference proteome; Transferase.
FT   CHAIN           1..1797
FT                   /note="Non-reducing polyketide synthase nscA"
FT                   /id="PRO_0000437894"
FT   DOMAIN          1720..1797
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          17..256
FT                   /note="N-terminal acylcarrier protein transacylase domain
FT                   (SAT)"
FT                   /evidence="ECO:0000255"
FT   REGION          395..828
FT                   /note="Ketosynthase (KS) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          931..1251
FT                   /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1318..1637
FT                   /note="Product template (PT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1663..1723
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1663..1687
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1696..1711
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        565
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   MOD_RES         1757
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1797 AA;  196324 MW;  0A6C1A4558819BA5 CRC64;
     MDSALQRVIF FGNEFPSDDL KDLFRRLYQH SKDRRFRLLS AFLEESTTVL KDEIAKLPWP
     LKELVPPFNS VLDLADVDFR QGPLGAAMES SMLTILELGM FIGHYQAEDV EWDLIPERTL
     LAGLSIGILA AAAVALSSSL ADVSKNGAEA VRVSFRLGIY VADISSKLET PQSDGTLKSW
     AHVVTEMTQA SVQDELNQFN TDTHSPELTK VFISAADKTS VSVSGPPSRV KAAFQHSPIL
     RYSKSLPLPV YDGLCHASHL YTRSDIDAII NCAESVIKPD RSVRLALLSS QTGKPFVAKA
     ASELFLEIGT ELLTGTIYLD NVTAGIIEHF KLQSEAATKC RIDSFRTSLV LRGIHSAVEA
     HFAEEQQQFI RCDLVCWVHK DFGPRQPRSH ASSKLAIVGM ACRLPGGAND LDLFWKLLED
     GRDTLTTVPV DRFDLNTHYD PTGKTENATQ TPYGNFIDRP GYFDAGFFNM SPREAEQTDP
     MQRLALVTAY EAMEMAGVVP GRTPSTHPSR IGTFYGQASD DWRELNASQN ISTYAVPGGE
     RAFANGRINY FFKFSGPSFN LDTACSSGLA AVQAACSALW AGEIDTAIAG GLNVITDPDN
     YCGLGNAHFL SKTGQCKVWD KDADGYCRAD GIGSVVIKRL EDAEADNDNI LAVVLGACTN
     HSAEAISITH PHAGAQKANY RQVLHQAGVN PIDVSYIELH GTGTQAGDAV ESESVSDIFA
     PVTPRRRPDQ RLHLGAVKSN IGHGEAAAGI ASLLKALLVY QKNMIPMHIG IKSEINPTIP
     KDLERRNVGL AMQNTPWPRV EGKKRLAVVN SFGAHGGNTT LLLEDAPEMV KAQNPEDRIT
     HSVLLSAKSK KSLQANMESL LSYLDQHPET NLADLAYTTS SRRMHHNMRF GTAVSCIPAL
     QKALRSQLDN TNFASEVRPI PNEAPSVVLA FTGQGAYYSG MGRELFSEFP YFRSQVQQLD
     QLAQRLGFPS VVPVIDGSIE DSSKSTILTQ LSVVILEIAL ARFWSLLGVS ISAVIGHSLG
     EYAALAVAGV ISAADAIYLV GRRARLVEER CTLGSHSMLS VRASEDAIQQ MLASGPDTAA
     IEYEVSCCNT NQDTVIGGLK DEINDIRKAL EAKSIKCTLL DVPYAFHTAQ MDPILDDLEA
     FAAHVPFNAP SIPVLSPLLA TAIFDVKSLN ANYLRRAARE TVDFAAAIEA AQDMGLVDSK
     TVWIDVGPHP ICAGLVRGMI PSVSVVSSCR RNEDSIATIC KSLVTLHLAG LTPCWAEFFK
     PRECEYSLLH LPKYRWNETN YWIPYIGTWT LDKAHLKHGT KPMTPFSLSM SRPSALRTSL
     IHQITAETIE STTATLHTIS DMQHPDFLEA IQGHTMNKCG VATSSIWSDM AFTVGEYLYR
     LLMPNVKDVH MNLTDVEVLH AQVASKTRGS IQPLVLQAHL DLSTNSMCLS WFNADGETGE
     CAAESFATAT VRFEDPAAWK KEWARLAHLV RGRIEALEQR AVEGKASRLS KPLAYALFKN
     VVDYADRYRG MDSVVLDELE AMAEVTLVPE RHGTWHTPPH WIDSVSHLAG LVMNGSDASN
     TRDYFFVTPG CDSFRLLNKL EPGAQYRSYV RMFPLLEDPN MHGGDVYILQ GEEIVGMVGM
     IRFRRVPRLL MDRFFSPPTT TSVVGPAPPV VSAATKTHGI TQSVPEISAP SPSIVVSDST
     ANNTLTDKLP VPVPRLASSS ESSTPKESPI ATPPESESAE PLGNTVSQCL RLMARETGLE
     VEALTGDASF VQLGVDSLMS LVLSEKFRAE LGVEIKSSLF LECPTIGEMT AWIEEYC